(A shortened excerpt from Fatand Cholesterol are GOOD for You!)
Most people ‘know’ thathigh cholesterol is something to be afraid of and that the most important thingto do to avoid a heart attack is to lower one’s cholesterol as much aspossible. But did you know that high cholesterol protects you against infectiousdiseases, which most probably explain that high cholesterol is associated withlongevity? With these facts min mind, why should we care about high cholesterol?
Oldpeople withhigh cholesterol live the longest. This statement seems so incredible that it takes along time to clear one´s brainwashed mind, at least for those who haven’tread this book, to fully understand its importance. Yet the fact that peoplewith high cholesterol live the longest emerges clearly from many scientificpapers.1
WhyHigh Cholesterol Is GoodIn certain aspects low cholesterol is worse than highcholesterol. Already fifteen years ago American researchers found that lowcholesterol predicts an increased risk of dying from diseases of the stomach,the intestines and the lungs.2Most ofsuch diseases are infectious. Therefore, a relevant question is whether it isthe infection that lowers cholesterol or the low cholesterol that predisposes toinfectious diseases You have probably already guessed what the directors of thecholesterol campaign have said, but is it true?
To answer that question the same researchers followed more than 100,000 healthyindividuals in the San Francisco area for fifteen years. At the end of the studythey noted that those who had low cholesterol at the start of the study had beenadmitted more often to hospital because of an infectious disease.3,4 Thisfinding cannot be explained away with the argument that the infection had causedcholesterol to go down, because how could low cholesterol, recorded when thesepeople had no evidence of infection, be caused by a disease they had not yetencountered? Isn’t it much more likely that low cholesterol in some way madethem more vulnerable to infection? Much evidence exists to support thatinterpretation.
To answer that question the same researchers followed more than 100,000 healthyindividuals in the San Francisco area for fifteen years. At the end of the studythey noted that those who had low cholesterol at the start of the study had beenadmitted more often to hospital because of an infectious disease.3,4 Thisfinding cannot be explained away with the argument that the infection had causedcholesterol to go down, because how could low cholesterol, recorded when thesepeople had no evidence of infection, be caused by a disease they had not yetencountered? Isn’t it much more likely that low cholesterol in some way madethem more vulnerable to infection? Much evidence exists to support thatinterpretation.
Low Cholesterol Predisposes To HIV And AIDS
Young, unmarried men with a previous sexually transmitted disease or liverdisease run a much greater risk of becoming infected with HIV virus than otherpeople. This was what a group of Minnesota researchers found by following suchpeople for several years. Those who had low cholesterol at the beginning of thestudy were twice as likely to test positive for HIV compared with those with thehighest cholesterol.5
Similar results came from another study of more than 300,000 young andmiddle-aged men.After sixteenyears four times more in the low-cholesterol group had died from AIDS comparedwith the high-cholesterol group.6
Young, unmarried men with a previous sexually transmitted disease or liverdisease run a much greater risk of becoming infected with HIV virus than otherpeople. This was what a group of Minnesota researchers found by following suchpeople for several years. Those who had low cholesterol at the beginning of thestudy were twice as likely to test positive for HIV compared with those with thehighest cholesterol.5
Similar results came from another study of more than 300,000 young andmiddle-aged men.After sixteenyears four times more in the low-cholesterol group had died from AIDS comparedwith the high-cholesterol group.6
Smith-Lemli-Opitz SyndromeThebenefit of high cholesterol also appears from studies of children with theSmith-Lemli-Opitz syndrome. They are born with very low cholesterol because anenzyme that is necessary for the body’s synthesis of cholesterol does notfunction properly. Most children with this syndrome are either stillborn or theydie early because of serious malformations of the brain. Those who survive areimbecile or autistic, they have extremely low cholesterol, and they suffer fromfrequent and severe infections. However, if they are given extra cholesterol oreggs in their diet, their cholesterol goes up, their infections become lessserious and less frequent, and their autistic and aggressive behavior improves.7
Thelipoproteins
Oneof the many reasons not to name LDL as bad is that the lipoproteins have otherimportant functions. One of them is to take care of microorganisms and theirtoxic products.
Staphylococcusaureus α-toxinis the most toxic substance produced by strains of the disease-promotingbacteria called staphylococci. It is able to destroy all kinds of human cells,including red blood cells. For instance, if minute amounts of the toxin areadded to a test tube with red blood cells dissolved in salt water, the blood ishemolyzed, that is, the membranes of the red blood cells burst and hemoglobinfrom the interior of the cells leaks out into the solvent. Dr. Bhakdi and histeam mixed purified α-toxin with human serum (the fluid in which the bloodcells reside) and now the toxic effect ofα-toxinalmost disappeared. By various complicated methods they identified theprotective substance in human serum as LDL, the carrier of the “bad”cholesterol. In accordance, nothing happened when they mixed α-toxin withpurified human LDL.
Dr. Willy Flegeland his co-workers at Heidelberg University in Germany studied bacterial toxinsin another way. As mentioned above, one of the effects of bacterial toxins isthat they stimulate white blood cells to produce cytokines, hormones that startthe inflammatory processes. The German researchers found that this effectdisappeared almost completely if the toxin was mixed with purified LDL beforethey added the white blood cells to the test tubes.8,9 Obviously, LDLwas able to neutralize the bacterial toxins.
Oneof the many reasons not to name LDL as bad is that the lipoproteins have otherimportant functions. One of them is to take care of microorganisms and theirtoxic products.
Staphylococcusaureus α-toxinis the most toxic substance produced by strains of the disease-promotingbacteria called staphylococci. It is able to destroy all kinds of human cells,including red blood cells. For instance, if minute amounts of the toxin areadded to a test tube with red blood cells dissolved in salt water, the blood ishemolyzed, that is, the membranes of the red blood cells burst and hemoglobinfrom the interior of the cells leaks out into the solvent. Dr. Bhakdi and histeam mixed purified α-toxin with human serum (the fluid in which the bloodcells reside) and now the toxic effect ofα-toxinalmost disappeared. By various complicated methods they identified theprotective substance in human serum as LDL, the carrier of the “bad”cholesterol. In accordance, nothing happened when they mixed α-toxin withpurified human LDL.
Dr. Willy Flegeland his co-workers at Heidelberg University in Germany studied bacterial toxinsin another way. As mentioned above, one of the effects of bacterial toxins isthat they stimulate white blood cells to produce cytokines, hormones that startthe inflammatory processes. The German researchers found that this effectdisappeared almost completely if the toxin was mixed with purified LDL beforethey added the white blood cells to the test tubes.8,9 Obviously, LDLwas able to neutralize the bacterial toxins.
AnimalExperiments
The immune systems in various mammals including human beings have manysimilarities. Therefore, it is interesting to see what experiments with rats andmice can tell us. Professor Kenneth Feingold and his group at the University ofCalifornia have published some interesting studies. In one of them they loweredLDL-cholesterol in rats by drugs with the result that they died much easierafter an injection of bacterial toxins. The high mortality was not due to thecholesterol-lowering drug because, if they gave the animals an injection ofhuman lipoproteins just before the experiment, they survived10
In another experiment, researchers from the Netherlands injected bacteria ortheir toxins into normal mice, and into mice with high cholesterol. Whereas allnormal mice died, most of the mice with high cholesterol survived.11
Many of the roles played by the lipoprotein LDL are shared byHDL as well. This should not be too surprising considering that highHDL-cholesterol is associated with cardiovascular health and longevity. Butthere is more.
Triglycerides, molecules consisting of three fatty acids linked to a moleculenamed glycerol, are insoluble in water and are therefore carried through theblood inside lipoproteins, just as cholesterol. All lipoproteins carrytriglycerides, but most of them are carried by the VLDL, the largest lipoproteinin our blood.
For many years it has been known that patientssuffering from sepsis, a life-threatening condition caused by bacterial growthin the blood, have high levels of triglycerides. The serious symptoms of sepsisare due to bacterial toxins, most often produced by gut bacteria. Now to theinteresting point. Solutions rich in triglycerides are also able to protectexperimental animals from the dangerous effects of bacterial toxins, which meansthat the high level of triglycerides seen in sepsis is not a bad thing, but anormal response to infection.12 Usually sepsis bacteria come from theguts. It is therefore fortunate that the blood draining the guts is especiallyrich in triglycerides.
The immune systems in various mammals including human beings have manysimilarities. Therefore, it is interesting to see what experiments with rats andmice can tell us. Professor Kenneth Feingold and his group at the University ofCalifornia have published some interesting studies. In one of them they loweredLDL-cholesterol in rats by drugs with the result that they died much easierafter an injection of bacterial toxins. The high mortality was not due to thecholesterol-lowering drug because, if they gave the animals an injection ofhuman lipoproteins just before the experiment, they survived10
In another experiment, researchers from the Netherlands injected bacteria ortheir toxins into normal mice, and into mice with high cholesterol. Whereas allnormal mice died, most of the mice with high cholesterol survived.11
Many of the roles played by the lipoprotein LDL are shared byHDL as well. This should not be too surprising considering that highHDL-cholesterol is associated with cardiovascular health and longevity. Butthere is more.
Triglycerides, molecules consisting of three fatty acids linked to a moleculenamed glycerol, are insoluble in water and are therefore carried through theblood inside lipoproteins, just as cholesterol. All lipoproteins carrytriglycerides, but most of them are carried by the VLDL, the largest lipoproteinin our blood.
For many years it has been known that patientssuffering from sepsis, a life-threatening condition caused by bacterial growthin the blood, have high levels of triglycerides. The serious symptoms of sepsisare due to bacterial toxins, most often produced by gut bacteria. Now to theinteresting point. Solutions rich in triglycerides are also able to protectexperimental animals from the dangerous effects of bacterial toxins, which meansthat the high level of triglycerides seen in sepsis is not a bad thing, but anormal response to infection.12 Usually sepsis bacteria come from theguts. It is therefore fortunate that the blood draining the guts is especiallyrich in triglycerides.
Highcholesterol protects against allergyChildrenwith allergic problems, such as asthma and hay fever, have lower cholesterolthan healthy children. As allergic diseases have become more common and is stillincreasing in the Western world it is tempting to suggest that the cause is theincreasing consumption of the polyunsaturated vegetable oils of the omega-6 type,because these oils are known to stimulate inflammatory processes, and allergy isa kind of inflammation. But there is room for another explanation.
At the Skin andAllergy Hospital in Helsinki, Finland Dr.Maria Pesonen and her co-workersfollowed 200 children from their birth to their 20 year anniversary.13They found that the children with allergic disorders had lower total and LDLcholesterol than the others. The difference was obvious already at a time whereall the children were breastfed. Thus, the difference could not be explained bytheir dietary habits. The researchers had no explanation for their observation,but if the lipoproteins are able to bind microbial products, it seems not toofar-fetched to assume that they can bind other molecules as well, for instanceallergens, those molecules that starts the allergic reactions.
At the Skin andAllergy Hospital in Helsinki, Finland Dr.Maria Pesonen and her co-workersfollowed 200 children from their birth to their 20 year anniversary.13They found that the children with allergic disorders had lower total and LDLcholesterol than the others. The difference was obvious already at a time whereall the children were breastfed. Thus, the difference could not be explained bytheir dietary habits. The researchers had no explanation for their observation,but if the lipoproteins are able to bind microbial products, it seems not toofar-fetched to assume that they can bind other molecules as well, for instanceallergens, those molecules that starts the allergic reactions.
Isfamilial hypercholesterolemia a disease?
“The more LDL there is in the blood, the more rapidly atherosclerosis develops.”
This was the main conclusion of the American NobelPrice-winners, Joseph Goldstein and Michael Brown.14 They discoveredthat the cells of people with familial hypercholesterolemia had difficultiestaking in cholesterol from the blood because of a defect in the LDL-receptor,the mechanism that transports these vital molecules into the cells. This was thereason why cholesterol was much higher than normal in these people. People withfamilial hypercholesterolemia also have more atherosclerosis than normal andsome of them do die early in life from heart disease. It was therefore not toofar-fetched for Goldstein and Brown to draw the conclusion they did, and also toassume that it was applicable to the rest of mankind. They were awarded theNobel Prize in 1985 for their discovery, and many other researchers share theirview.
Their finding is certainly interesting, a result ofcareful scientific work. Unfortunately, the conclusion they drew was too hasty.In fact, there are benefits associated with this condition, which is why Ideliberately refer to individuals with familial hypercholesterolemia as people,not as patients. What is even more surprising is that the reason why some ofthem die at a young age from heart disease is not their high cholesterol, butsomething else. I shall come back to that.
InEngland The Simon Broome Familial Hyperlipidaemia Register Group have followedalmost 3000 people with familial hypercholesterolemia for many years. At the most recent control they found that 102 of them, or 3.6 % had diedfrom a heart attack. By analyzing mortality of the same age group in the Englishpopulation they calculated that the expected number should have been 40, or 1.4%. On the other hand, fewer had died from other causes, 112 against the expectednumber 193, or 4 % against 6.8 %. For instance, only half as many had died fromcancer.30 If you add the figures and compare them you will see thatpeople with familial hypercholesterolemia live at least as long as other people,if not longer. A little more die from heart disease, but fewer die from cancerand other diseases.
The authors of the scientific report stressed that theparticipants in their study were admitted because all of them had closerelatives who had died at a young age. Cholesterol screening often identifiesold people with familial hypercholesterolemia who have no such relatives. Theauthors therefore suggested that if the participants had been representative forall people with familial hypercholesterolemia, their mortality would have beeneven lower.
In Finland, Professor Tatu Miettinen and Dr. HelenaGylling studied about one hundred individuals with familialhypercholesterolemia.16 Fourteen to seventeen years later, 30 haddied, 26 because of a heart attack and four of other causes. On average, initialLDL cholesterol was the same among those who had died and those who still werealive. If high LDL cholesterol was the most important cause of atherosclerosisand heart disease, as postulated by Nobel Award winners Goldstein and Brown,then we should have expected higher cholesterol in those who died, but thatwasn’t the case. Many other researchers have confirmed the Finnish findings.17-23Another conflicting observation is the fact thatpeople with familial hypercholesterolemia have normal cerebral arteries, eventhough the same cholesterol-rich blood flows through their brain as through therest of their body.25
“The more LDL there is in the blood, the more rapidly atherosclerosis develops.”
This was the main conclusion of the American NobelPrice-winners, Joseph Goldstein and Michael Brown.14 They discoveredthat the cells of people with familial hypercholesterolemia had difficultiestaking in cholesterol from the blood because of a defect in the LDL-receptor,the mechanism that transports these vital molecules into the cells. This was thereason why cholesterol was much higher than normal in these people. People withfamilial hypercholesterolemia also have more atherosclerosis than normal andsome of them do die early in life from heart disease. It was therefore not toofar-fetched for Goldstein and Brown to draw the conclusion they did, and also toassume that it was applicable to the rest of mankind. They were awarded theNobel Prize in 1985 for their discovery, and many other researchers share theirview.
Their finding is certainly interesting, a result ofcareful scientific work. Unfortunately, the conclusion they drew was too hasty.In fact, there are benefits associated with this condition, which is why Ideliberately refer to individuals with familial hypercholesterolemia as people,not as patients. What is even more surprising is that the reason why some ofthem die at a young age from heart disease is not their high cholesterol, butsomething else. I shall come back to that.
InEngland The Simon Broome Familial Hyperlipidaemia Register Group have followedalmost 3000 people with familial hypercholesterolemia for many years. At the most recent control they found that 102 of them, or 3.6 % had diedfrom a heart attack. By analyzing mortality of the same age group in the Englishpopulation they calculated that the expected number should have been 40, or 1.4%. On the other hand, fewer had died from other causes, 112 against the expectednumber 193, or 4 % against 6.8 %. For instance, only half as many had died fromcancer.30 If you add the figures and compare them you will see thatpeople with familial hypercholesterolemia live at least as long as other people,if not longer. A little more die from heart disease, but fewer die from cancerand other diseases.
The authors of the scientific report stressed that theparticipants in their study were admitted because all of them had closerelatives who had died at a young age. Cholesterol screening often identifiesold people with familial hypercholesterolemia who have no such relatives. Theauthors therefore suggested that if the participants had been representative forall people with familial hypercholesterolemia, their mortality would have beeneven lower.
In Finland, Professor Tatu Miettinen and Dr. HelenaGylling studied about one hundred individuals with familialhypercholesterolemia.16 Fourteen to seventeen years later, 30 haddied, 26 because of a heart attack and four of other causes. On average, initialLDL cholesterol was the same among those who had died and those who still werealive. If high LDL cholesterol was the most important cause of atherosclerosisand heart disease, as postulated by Nobel Award winners Goldstein and Brown,then we should have expected higher cholesterol in those who died, but thatwasn’t the case. Many other researchers have confirmed the Finnish findings.17-23Another conflicting observation is the fact thatpeople with familial hypercholesterolemia have normal cerebral arteries, eventhough the same cholesterol-rich blood flows through their brain as through therest of their body.25
Amissing linkThegenetic aberrations in people with familial hypercholesterolemia are morecomplicated than Brown and Goldstein assumed. For instance, in a study of 2400such individuals, Dr. Angelique Jansen at the University of Amsterdam found that variations of the prothrombin gene were associated with anincreased risk of heart disease in these people.26 Prothrombin is asubstance necessary for blood coagulation and an abnormal prothrombin gene maylead to the production of too much of this substance. The result is an increasedtendency to coagulation and clot formation. Thus, some individuals with familialhypercholesterolemia may form arterial clots more easily than other people, notbecause of their high cholesterol, but because of an abnormal coagulationsystem.
Heartpatients with familial hypercholesterolemia more often have high concentrationsof fibrinogen and factor VIII in their blood than healthy people with familialhypercholesterolemia. Also these substances participate in the coagulationprocess, and too much of them may stimulate to clot formation. And again,whereas the heart patients had much higher concentrations of fibrinogen andfactor VIII, their total and LDL cholesterol did not differ from those measuredin healthy people with familial hypercholesterolemia.27
Inearlier times, people with familial hypercholesterolemia lived longerthan other people! Dutch researchers tracked the ancestors of people withfamilial hypercholesterolemia and identified 412 individuals with a 50 percentchance of having this genetic abnormality. They also searched official recordsof deaths and found that the longevity of those with a family history of thisgenetic aberration was not lower before the year 1900; in fact, on average theylived longer than other people. As the most common cause of death at that timewas infectious disease, the authors suggested that high cholesterol protectsagainst infection.28
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